Elevated serum homocysteine has been identified in multiple epidemiologic studies to be an independent risk factor for cardiovascular disease, stroke, depression, osteoporosis and dementia. The only known method to reduce homocysteine is through vitamin supplementation with folate, B12, and B6. Of these three vitamins, folate supplementation leads to the greatest homocysteine reduction with only slight additional benefit with B12 and B6 supplementation. In the U.S., federally-mandated folate supplementation of the food supply has been in effect since 1998, which has led to lower homocysteine levels in U.S. cohort studies. Therefore, one would expect to find homocysteine levels less responsive to vitamin supplementation in the U.S. population since the food supply is already supplemented with folate.
In a multi-centered clinical trial conducted in Switzerland and the U.S., 553 patients with known cardiovascular disease randomized to vitamin therapy of folate, B12, and B6 showed about a 30% reduction in homocysteine levels compared with subjects randomized to placebo. The vitamin therapy group also showed improved cardiovascular outcomes. However, there is an ongoing need for a method to reduce homocysteine levels in individuals.